New analyses show the effect of OCREVUS on reducing the risk of disability progression is associated with exposure and lower B-cell levels

Long-term data in RMS and PPMS show that earlier treatment with OCREVUS significantly reduced the risk of permanent disability progression

Over 100,000 people have been treated with OCREVUS globally, in clinical trial and real-world settings; data presented at the AAN Annual Meeting highlights a consistent and favorable benefit-risk profile

South San Francisco, CA -- May 7, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new OCREVUS® (ocrelizumab) data in relapsing and primary progressive multiple sclerosis (MS) were presented at the 71st American Academy of Neurology (AAN) Annual Meeting from May 4-10 in Philadelphia, Pennsylvania. New analyses on OCREVUS show its effect on reducing the risk of disability progression is associated with higher exposure to the medicine and lower B-cell levels, and show the positive impact of OCREVUS in significantly reducing disability progression.

With rapidly growing real-world experience and more than 100,000 patients treated globally, OCREVUS is the first and only therapy with six-month dosing approved for both relapsing MS (RMS), (including RRMS and active, or relapsing, secondary progressive MS) and primary progressive MS (PPMS). Additionally, new safety data presented at AAN representing 4,501 patients with RMS and PPMS and 12,559 patient years of exposure to OCREVUS, across all OCREVUS clinical trials, remain consistent with the medicine’s favorable benefit-risk profile.

“These are the first data to show that higher OCREVUS exposure is associated with greater control of disability progression without impacting safety,” said Stephen Hauser, M.D., chair of the Scientific Steering Committee of the OPERA studies and director of the Weill Institute for Neurosciences at the University of California, San Francisco. “These analyses, along with long-term data that show OCREVUS reduced the risk of permanent disability progression, create a compelling case for initiating therapy early in the disease course and provide important information that clinicians can use to inform treatment decisions.”

New data from pharmacokinetic, pharmacodynamic and exposure analyses – or how OCREVUS is processed in an individual’s body over time – show higher exposure to OCREVUS correlated with lower B-cell levels and lower rates of disability progression in patients. In patients with RMS, OCREVUS reduced the risk of 24-week confirmed disability progression (CDP) at all exposure levels compared with interferon beta-1a. There was lower risk of disability progression with higher exposure to OCREVUS.

A similar pattern was observed for patients with PPMS, in which OCREVUS reduced the risk of 24-week CDP at all exposure levels compared with placebo. OCREVUS reduced T1 gadolinium-enhancing and new/enlarging T2 MRI lesions to nearly undetectable levels in RMS and PPMS patients and reduced annualized relapse rates to low levels (0.13-0.18) in RMS patients across all exposure segments. Notably, safety findings remained consistent across all OCREVUS exposure levels, suggesting that higher exposure does not increase the likelihood of adverse events.

Long-term data, of over five years, from the Phase III OPERA and ORATORIO open-label extension (OLE) trials in RMS and PPMS, show that earlier treatment with OCREVUS significantly reduced the risk of permanent disability progression and this effect was sustained over time. In the OPERA OLE, the proportion of RMS patients with 48-week CDP was lower for those treated with continuous OCREVUS (total of five years on OCREVUS) compared with patients who switched to OCREVUS after two years of interferon beta-1a treatment in the double-blind period (total of three years on OCREVUS) (10.4% vs. 15.7%; p=0.004). In the ORATORIO OLE, the proportion of PPMS patients with 48-week CDP was lower in those treated with continuous OCREVUS over five and a half years compared with patients who switched to OCREVUS from placebo after the 120-week double-blind period (43.7% vs. 53.1%; p=0.03).

Additionally, interim results of the Phase III Ocrelizumab Biomarker Outcome Evaluation (OBOE) study show that OCREVUS reduced the presence of a nerve cell damage and inflammation biomarker in serum and cerebrospinal fluid at 12, 24 and 52 weeks in patients with RMS. These one-year data add to the growing body of evidence to identify biomarkers of disease progression in MS and the benefit of OCREVUS on these markers.

OCREVUS is now approved in 85 countries across North America, South America, the Middle East, Eastern Europe, as well as in Australia, Switzerland and the European Union.

Follow Genentech on Twitter via @Genentech and keep up to date with AAN 2019 Annual Meeting news and updates by using the hashtag #AANAM.

About the OPERA I and OPERA II studies in relapsing forms of MS

OPERA I and OPERA II are Phase III, randomized, double-blind, double-dummy, global multi-center studies evaluating the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months) compared with interferon beta-1a (44 mcg administered by subcutaneous injection three times per week) in 1,656 people with relapsing forms of MS. In these studies, relapsing MS (RMS) was defined as relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses. A similar proportion of patients in the OCREVUS group experienced serious adverse events and serious infections compared with patients in the high-dose interferon beta-1a group in the RMS studies.

About the ORATORIO study in primary progressive MS

ORATORIO is a Phase III, randomized, double-blind, global multi-center study evaluating the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months; given as two 300 mg infusions two weeks apart) compared with placebo in 732 people with primary progressive MS (PPMS). The blinded treatment period of the ORATORIO study continued until all patients had received at least 120 weeks of either OCREVUS or placebo and a predefined number of confirmed disability progression (CDP) events was reached overall in the study. A similar proportion of patients in the OCREVUS group experienced adverse events and serious adverse events compared with patients in the placebo group in the PPMS study.

About multiple sclerosis

Multiple sclerosis (MS) is a chronic disease that affects nearly one million people in the U.S., for which there is currently no cure. MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the brain, spinal cord and optic nerves, causing inflammation and consequent damage. This damage can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to disability. Most people with MS experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.

Relapsing-remitting MS (RRMS) is the most common form of the disease and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. Approximately 85 percent of people with MS are initially diagnosed with RRMS. The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive MS (SPMS), in which they experience steadily worsening disability over time. Relapsing forms of MS (RMS) include people with RRMS and people with SPMS who continue to experience relapses. Primary progressive MS (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15 percent of people with MS are diagnosed with the primary progressive form of the disease. Until the FDA approval of OCREVUS, there had been no FDA approved treatments for PPMS.

People with all forms of MS experience disease activity – inflammation in the nervous system and permanent loss of nerve cells in the brain – even when their clinical symptoms aren’t apparent or don’t appear to be getting worse. An important goal of treating MS is to reduce disease activity as soon as possible to slow how quickly a person’s disability progresses. Despite available disease-modifying treatments (DMTs), some people with RMS continue to experience disease activity and disability progression.

About OCREVUS® (ocrelizumab)

OCREVUS is a humanized monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with multiple sclerosis (MS). Based on preclinical studies, OCREVUS binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.

OCREVUS is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.

Important Safety Information

What is OCREVUS?

OCREVUS is a prescription medicine used to treat adults with relapsing or primary progressive forms of multiple sclerosis.

It is not known if OCREVUS is safe or effective in children.

Who should not receive OCREVUS?

Do not receive OCREVUS if you have an active hepatitis B virus (HBV) infection.

Do not receive OCREVUS if you have had a life threatening allergic reaction to OCREVUS. Tell your healthcare provider if you have had an allergic reaction to OCREVUS or any of its ingredients in the past.

What is the most important information I should know about OCREVUS?

OCREVUS can cause serious side effects, including:

Infusion reactions: OCREVUS can cause infusion reactions that can be serious and require you to be hospitalized. You will be monitored during your infusion and for at least 1 hour after each infusion of OCREVUS for signs and symptoms of an infusion reaction. Tell your healthcare provider or nurse if you get any of these symptoms:

itchy skin

rash

hives

tiredness

coughing or wheezing

trouble breathing

throat irritation or pain

feeling faint

fever

redness on your face (flushing)

nausea

headache

swelling of the throat

dizziness

shortness of breath

fatigue

fast heart beat

These infusion reactions can happen for up to 24 hours after your infusion . It is important that you call your healthcare provider right away if you get any of the signs or symptoms listed above after each infusion.

If you get infusion reactions, your healthcare provider may need to stop or slow down the rate of your infusion.

Infection:

OCREVUS increases your risk of getting upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes infections. Tell your healthcare provider if you have an infection or have any of the following signs of infection including fever, chills, a cough that does not go away, or signs of herpes (such as cold sores, shingles, or genital sores). These signs can happen during treatment or after you have received your last dose of OCREVUS. If you have an active infection, your healthcare provider should delay your treatment with OCREVUS until your infection is gone.

Progressive Multifocal Leukoencephalopathy (PML): Although no cases have been seen with OCREVUS treatment in clinical trials, PML may happen with OCREVUS. PML is a rare brain infection that usually leads to death or severe disability. Tell your healthcare provider right away if you have any new or worsening neurologic signs or symptoms. These may include problems with thinking, balance, eyesight, weakness on 1 side of your body, strength, or using your arms or legs.

Hepatitis B virus (HBV) reactivation: Before starting treatment with OCREVUS, your healthcare provider will do blood tests to check for hepatitis B viral infection. If you have ever had hepatitis B virus infection, the hepatitis B virus may become active again during or after treatment with OCREVUS. Hepatitis B virus becoming active again (called reactivation) may cause serious liver problems including liver failure or death. Your healthcare provider will monitor you if you are at risk for hepatitis B virus reactivation during treatment and after you stop receiving OCREVUS.

Weakened immune system: OCREVUS taken before or after other medicines that weaken the immune system could increase your risk of getting infections.

Before receiving OCREVUS, tell your healthcare provider about all of your medical conditions, including if you:

have ever taken, take, or plan to take medicines that affect your immune system, or other treatments for MS.

have ever had hepatitis B or are a carrier of the hepatitis B virus.

have had a recent vaccination or are scheduled to receive any vaccinations.

When possible, you should receive any ‘non-live’ vaccines at least 2 weeks before you start treatment with OCREVUS. If you would like to receive any non-live (inactivated) vaccines, including the seasonal flu vaccine, while you are being treated with OCREVUS, talk to your healthcare provider.

If you are pregnant or planning to become pregnant talk to your doctor about vaccinations for your baby, as some precautions may be needed.

are pregnant, think that you might be pregnant, or plan to become pregnant. It is not known if OCREVUS will harm your unborn baby. You should use birth control (contraception) during treatment with OCREVUS and for 6 months after your last infusion of OCREVUS.

are breastfeeding or plan to breastfeed. It is not known if OCREVUS passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take OCREVUS.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

For additional safety information, please see the OCREVUS full Prescribing Information and Medication Guide.

About Genentech in neuroscience

Neuroscience is a major focus of research and development at Genentech and Roche. The company’s goal is to develop treatment options based on the biology of the nervous system to help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche have more than a dozen investigational medicines in clinical development for diseases that include multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.